Male Reproductive System Flashcards
Where are sperm formed?
the testes
What is acrosome?
The cap on the head of sperm
What are the two functions of the testes?
Gametogenic and endocrine. (Produces sperm and hormones)
What is the thick capsule that surround the testes?
Tunica Albuginea
What are lobules?
Sections of division in the testis. Each has 1-3 seminiferous tubules.
What are seminiferous tubules?
Long (~0.25-0.5 miles per testis), highly convoluted tubules that are the site of spermatogenesis
What is spermatogenesis?
Formation, development, and maturation of the male gamete.
Where do sperm move once they are formed?
The Rete Testes, collecting tubules (efferent ductules, epididymis, and then to vas deferens (sequential). They are stored in distal epididymis and stored until ejaculate. They undergo modification or maturation during storage that makes them fertile.
What are Leydig cells?
endocrine cells that produce androgens/steroid hormone including Testosterone (which is the most active androgen hormone biologically). In males, they cause development and maintainance of secondary reproductive organs and influence certain secondary sex characteristics such as hair distribution and voice. Leydig cells are present outside seminiferous tubules.
What are seminiferous tubules lined with?
Seminiferous epithelium which is composed of 2 cell lines: sertoli cells and germ cells (at various stages of development). This is where sperm are produced.
What is a stem cell?
a cell that can divide without limit and whose progeny include more stem cells and cells destined to differentiate. Self Renew and Differentiate
What is the difference between symmetric and asymmetric division?
Schematic depicting the current understanding of determinants of the spermatogonial stem cell (SSC) niche in mammalian testes
Sertoli cells are known to dictate the formation of niche microenvironments and have been shown to produce the growth factors GDNF and FGF2 which regulate SSC proliferation and survival. Leydig cells are a source of CSF-1 which specifically regulates self-renewal of SSCs. The differentiation of SSCs is influenced by BMP4 and Neuregulin 1; however, the source of these factors is currently unknown. It is believed that upon differentiation from SSCs the resulting progenitor spermatogonia (i.e., Apr/Aal) migrate away from the niche and continue to develop as a cohort of maturing germ cells.
SERTOLI CELLS AND GERM LINE
Sertoli Cells:
- Somatic cells. Not part of germ line.
- Large Branched CElls; base of cell is on baement membrane and apex projects into lumen of tubule.
- They do not divide in the adult
- Functions:
A. Mechanical support for germ cells (Scaffold)
B. Probide lactate and pyruvate as energy sources for spermatids
C. Function in Spermiation (release of sperm into lumen)
D. Phagocytotic (remove debris from lumen)
E. Secretes Fluid in to lumen of Seminiferous Tubule
F. In Fetal Male, it secretes Mullerian Inhibiting Substance (MIS) (Antimullarian hormone - AMH) Which causes degeneration of the mullerian or paramesonephric ducts. Causes regression of some kinds of tumors (anticancer drug).
G. Secrete Androgen Binding Protein (Has a high affinity for androgens; keeps levels of testosterone high in seminiferous epithelium. Testosterone is needed for spermatogenesis).
Germ line in image
SPERMATOGENESIS
CONVERSION OF A SPERMATOGONIUM INTO 4 SPERM CELLS
OCCURS IN SEMINIFEROUS EPITHELIUM OF TESTES
SPERMATOGENESIS IS A TWO STEP PROCESS
A. NUCLEAR CHANGES = MEIOSIS - OCCUR FIRST
B. CYTOPLASMIC CHANGES = SPERMIOGENESIS
MEIOSIS - PRODUCES A SPERMATID WITH HAPLOID NUMBER OF CHROMOSOMES
SPERMIOGENESIS - SPERMATIDS DIFFERENTIATE INTO SPERM
A. ACQUIRE AND ACROSOME AT FRONT END
B. ACQUIRE A FLAGELLUM - MOTILE
C. STREAMLINED FOR FERTILIZATION
DIFFERENTIATION FROM SPERMATOGONIUM TO SPERM IN MAN TAKES 64 DAYS
MEIOSIS NUCLEAR EVENTS
N= NUMBER OF LIKE OR HOMOLOGOUS DNA STRANDS IN CELL
PLOIDY = LIKE OR HOMOLOGOUS CHROMOSOMES
HUMAN HAS 23 PAIRS OF CHROMOSOMES (22 AUTOSOMES AND 1 PAIR SEX CHROMOSOMES)
PGC DIVIDE BY MITOSIS BECOMING SPERMATOGONIA = 2N AND DIPLOID
MEIOSIS INVOLVES 2 CELL DIVISIONS:
- ALL 46 STRANDS OF DNA ARE REPLICATED = 4N AND DIPLOID
UPON DIVISION - ONE CHROMOSOME IN EACH PAIR GOES TO A DIFFERENT DAUGHTER CELL - NOW THESE CELLS ARE HAPLOID AND 2N
- CENTROMERE REPLICATES - GIVING TWO SINGLE STRANDED CHROMOSOMES FROM EACH DOUBLE STRANDED CHROMOSOME
AT NEXT DIVISION - ONE STRAND OF EACH CHROMOSOME GOES TO ONE OF TWO DAUGTHER CELLS = 1N AND HAPLOID
NON-DISJUNCTION- WHAT IF NON-DISJ SPERM FERTILIZE AN OOCYTE
EG FOR CHROMOSOME #21 - GET A TRISOMY = DOWNS SYNDROME
FOR EMPTY SPERM - MONOSOMY OF AN AUTOSOME - DEATH
What is the tunica albuginea?
A coating around the testes
H+E Stains
Hematoxylin stains nuclie blue, eosin stains cytoplasm red
What is seminiferous epithelium?
epithelium where sperm are produced. Stratafied tissue.
What does CSF1 do?
Causes division of stem cells
GDNF and FGF2 are:
from Sertoni cell.
Survival factors. Without these, stem cells undergo apoptosis.
MIS
Mullerian inhibiting substance causes female portion of rproductive tract to disappear in males
Spermiation:
release of mature sperm cells from seretoli cell into lumen
Spermiogenesis image
Acrosomal vescicle comes from secretions of the golgi apparatus. Proteins made in the rough endoplasmic reticulum end up pinching off the golgi apparatus and fusing together to wrap around the spermatid’s nucleus.
Centrioles are where the flagellum forms off.
The spermatid has a lot of excess cytoplasm, which is pinched off.
The mitochondria wrap around the flagellum, forming the midpiece.
Anatomy of a mature sperm
Anatomy of the head of a mature sperm
The acrosomal cap is the top and the equatorial region is pinched in.
Electron micrograph of a cross section of a flagellum
nine doublets with two cells in the center
Timeline of spermatogenesis
at 12 weeks development, testes are visible.
Seminiferous tubules are not active until puberty
Regulation of Spermatogenesis
FSH goes from the anterior pituitary gland to the bloodstream to the testes where it causes mitotic divison. Sertoli cells make androgen binding hormone (ABH increases testoterone levels around germ cells) and starts meiotic division
LH goes from the anterior pituitary gland to the bloodstream to the testes where it causes teh leydig cells to make testosterone which stimulates mitotic division
Reasons sperm counts are decreasing:
Xenoestrogen (Introduced into the environment by humans)
Drugs (MJ, alcohol, etc)
Bone regulating male fertility:
Osteocalcin from bones travels to the testes where it stimulates leydig cells to make testosterone:
“Interactions between bone and the reproductive system have until ow been thought to be limited to teh regulation of bone remodeling by the gonads. We now show that, in males, bone acts as a regulator of fertility. Using coculture assays, we demonstrate that osteoblasts are able to induce testosterone production by the testes, though they fail to influence estrogen production by the ovaries. Analyses of cell-specific loss- and gain-of-function models reveal that the osteoblast-derived hormone osteocalcin performs this endocrin function. By binding to a G protein-coupled receptor expressed in the Leydig cells of the testes, osteocalcin regulates in a CREB-dependent manner the expression of enzymens taht is required for testosterone synthesis, promoting germ cell survival. This study expands the physiological repertoire of osteocalcin and provides the first evidence that the skeleton is an endocrine regulator of reproduction.”
DEFECTS ASSOCIATED WITH SPERMATOGENESIS
NON-DISJUNCTION may occur at meiosis 1 or 2 (OOGENESIS TOO) –
NUMERICAL DEFECTS – ANEUPLOIDY = MOST COMMON
GENETIC ABNORMALITY IN HUMANS
DOWNS SYNDROME – TRISOMY 21
EXTRA COPY OF#21. MENTAL RETARDATION, CARDIAC DEFECTS, PREMATURE ALZHEIMERS
USUALLY CAUSED BY NON-DISJUNCTION OF CHROMOSOME 21 DURING MEIOSIS
1 IN 2000 FOR WOMEN UNDER 25 YRS, BUT INCREASES TO 1 IN 100 BY 40 YEARS
MAY ALSO BE CAUSED BY TRANSOLATION OF CHROMOSOME 21 TO 13, 14, OR 15 – UNBALANCED
MAY ALSO BE CAUSED BY NON-DISJUNCTION DURING MITOSIS IN EMRYO = MOSACIC
TURNERS SYNDROME – MONOSOMY (XO)
NON-DISJ –IN SPERM IS CAUSE IN 80% OF CASES
OTHERS CAUSED BY STRUCUTRAL ABNORMALITY IN X CHROMOSOME OR ARE MOSAICS
FEMALES ARE 45 X (LACK AN X) = MONOSOMY OF SEX CHROMOSOME. THESE MAY SURVIVE.
1/5000 IN LIVE BIRTHS; VERY COMMON IN ABORTED FETUSES
FAIL TO MATURE PROPERLY AT PUBERTY – ABSENT OVARIES, SHORT, WEBBED NECK,
KLINEFELTERS SYNDROME -47 XXY
IS CAUSED BY NON-DISJUNCTION OF XX CHROMOSOMES -XXY
MALES ARE INFERTILE, TESTICULAR ATROPHY, NO SPERM, HAVE FEMALE CHARACTERISTICS
HAVE MORE THAN ONE X CHROMOSOME- OCCURS 1/500
OTHER TRISOMIES:18 AND 13
MOSAICS - ALL OF ABOVE MAY BE MOSAICS. EG TURNERS MAY BE MIXTURE OF 46XX AND 45X
HAPPENS WHEN NON-DISJ OCCURS IN A SINGLE CELL DURING CLEAVAGE DIVISIONS (MITOTIC DIVISIONS)
Up to 40% of sperm from a semen sample can be defective. Normally 20-40% some have all defective.
KLINEFELTERS SYNDROME
47 XXYIS CAUSED BY NON-DISJUNCTION OF XX CHROMOSOMES -XXY
MALES ARE INFERTILE, TESTICULAR ATROPHY, NO SPERM, HAVE FEMALE CHARACTERISTICS
HAVE MORE THAN ONE X CHROMOSOME- OCCURS 1/500
OTHER DEFECTS OCCURRING DURING SPERMATOGENESIS
SPERMIOGENESIS
DEFECTIVE SPERM -
2 HEADED, NO ACROSOME
AZOOSPERMIA (no sperm)
OLIGOSPERMIA (few sperm…can be treated)
ABNORMAL SPERMIOGENESIS MAY PRODUCE ABNORMALLY SHAPED SPERM
TWO HEADS, TWO TAILS, NO TAILS, NO ACROSOME
EVEN IN NORMAL FERTILE MALES MANY SPERM ARE ABNORMAL (40%)
AZOOSPERMIA - NO SPERM ARE PRODUCED - MAY BE SEEN IN KLINEFELTER’S
OLIGOSPERMIA - LOW SPERM COUNT - ALSO SEEN IN KLINEFELTER’S - MADE BE FERTILE IF ASSISTED REPRODUCTION USED
Male Biological Clock
Epidemiological data suggest that as men age, the likelihood of them having a child with autism, schizophrenia or bipolar disorder increases.
Sperm arise from stem cells that may divide over 850 times by age 50. Mutations can occur with each division. Mutation rate in males higher than in females.
